NCT07830758 · Madrigal Pharmaceuticals, Inc.
Resmetirom in Patients With MASH and HFpEF
What this study is about
This Phase 1b conducted at multiple hospitals randomly assigned where neither patients nor doctors know which treatment is given compared against an inactive treatment study evaluates the safety, tolerability and hepatic how the drug affects the body effects of resmetirom in adults with metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF). Participants are randomly assigned 2:1 to resmetirom or placebo for 24 weeks.
View original scientific description
This Phase 1b multicenter randomized double-blind placebo-controlled study evaluates the safety, tolerability and hepatic pharmacodynamic effects of resmetirom in adults with metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF). Participants are randomized 2:1 to resmetirom or placebo for 24 weeks.
Interventions
DRUG
Resmetirom
Resmetirom (80 mg or 100 mg orally once daily based on body weight)
DRUG
Placebo
Matching placebo orally once daily
Primary outcome measures
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: From first dose through End of Study follow-up (28 days after last dose)
Incidence of treatment-emergent serious adverse events (SAES)
Time frame: From first dose through End of Study follow-up (28 days after last dose)
Change from baseline in physical examination findings assessed by investigator physical examination
Time frame: Baseline to Week 24
Physical examination findings will be assessed by the Investigator and include general appearance, skin, head and neck, heart, lungs, abdomen, extremities, and neuromuscular assessments. After Screening and successful Randomization, physical examinations may be targeted to evaluation of new symptoms or signs.
Change from baseline in body temperature
Time frame: Baseline to Week 24
Body temperature will be measure in °C, resting heart rate in beats per minute, respiratory rate in breaths per minute, systolic blood pressure in mmHg, and diastolic blood pressure in mmHg
Change from baseline resting heart rate
Time frame: Baseline to Week 24
Resting heart rate will be measured in beats per minute (bpm)
Change from baseline in respiratory rate
Time frame: Baseline to Week 24
Respiratory rate will be measured in breaths per minute.
Change from baseline in seated systolic blood pressure
Time frame: Baseline to Week 24
Resting seated systolic blood pressure will be measured in millimeters of mercury (mmHg)
Change from baseline in seated diastolic blood pressure
Time frame: Baseline to Week 24
Resting seated diastolic blood pressure will be measured in millimeters of mercury (mmHg)
Change from baseline in PR interval on 12-lead ECG in milliseconds (ms)
Time frame: Baseline to Week 24
Change from baseline in QRS interval on 12-lead ECG in milliseconds (ms)
Time frame: Baseline to Week 24
Change from baseline in heart rate on 12-lead ECG in beats per minute (bpm)
Time frame: Baseline to Week 24
Change from baseline in RR interval on 12-lead ECG in milliseconds (ms)
Time frame: Baseline to Week 24
Change from baseline in QT interval on 12-lead ECG in milliseconds (ms)
Time frame: Baseline to Week 24
Change from baseline in QT interval corrected using Bazett's formula (QTcB) in milliseconds (ms)
Time frame: Baseline to Week 24
Change from baseline in QT interval corrected using Fridericia's formula (QTcF) in milliseconds (ms)
Time frame: Baseline to Week 24
Number of participants with clinically significant abnormalities in hematology laboratory parameters
Time frame: Baseline to Week 24
Hematology laboratory parameters include hemoglobin, hematocrit, red blood cell count, white blood cell count, platelet count, red blood cell indices, and differential leukocyte counts. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.
Number of participants with clinically significant abnormalities in blood chemistry laboratory parameters
Time frame: Baseline to Week 24
Blood chemistry laboratory parameters include measures of hepatic function, renal function, glucose metabolism, pancreatic function, electrolytes, bilirubin, and serum proteins. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.
Number of participants with clinically significant abnormalities in urinalysis parameters
Time frame: Baseline to Week 24
Urinalysis parameters include pH, specific gravity, protein, glucose, ketones, bilirubin, blood, nitrite, urobilinogen, and leukocyte esterase. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.
Percent change from baseline in liver fat content measured by MRI-Proton Density Fat Fraction (MRI-PDFF)
Time frame: Baseline to Week 24
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Must be willing to participate in the study and provide written informed consent.
- Male and female adults ≥18 years of age.
- Suspected or confirmed diagnosis of fibrotic MASH suggested by the historical data and meets at least 1 criteria for fibrotic MASH
- Confirmed diagnosis of HFpEF
- Structural and/or functional heart disease based on echocardiographic evaluation.
- eGFR ≥45 mL/min/1.73 m2
- Female patients of reproductive potential are eligible if they have a negative serum pregnancy test (beta human chorionic gonadotropin), are not breastfeeding, and do not plan to become pregnant during the study and agree to use 1 highly effective birth control method during the study and for at least 30 days after study drug administration. Highly effective birth control methods include hormonal and non-hormonal intrauterine device, combination estrogen-progesterone hormonal contraception (oral, transdermal, or vaginal), tubal ligation, a vasectomized or sterile male partner, or sexual abstinence (defined as refraining from heterosexual intercourse), from Screening, throughout the study and for at least 30 days after study drug administration.
Exclusion criteria
- Patients with cirrhosis and other etiologies of chronic liver disease
- PEth value of ≥20 ng/mL measured at Screening OR history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
- Thyroid disease:
- Active hyperthyroidism
- Untreated clinical hypothyroidism defined by TSH \>7 IU/L with symptoms of hypothyroidism or \>10 IU/L without symptoms
- History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study
- Weight gain or loss \>5% total body weight within 12 weeks prior to randomization
- HbA1c \>9.0%
- Diagnosis of HCC
- MELD score ≥12, as determined at Screening, due to liver disease
- Hepatic decompensation or impairment.
- Has an active autoimmune disease, including actively treated lupus, rheumatoid arthritis, inflammatory bowel disease, or autoimmune hepatitis, requiring systemic treatment within the past 12 weeks or a documented history of clinically severe autoimmune disease, including autoimmune liver disease, or a syndrome that requires systemic steroids or immunosuppressive agents
- Serum ALT \>250 U/L
- Platelet count \<140,000/mm3. Patients with platelets \<140,000 and ≥120,000/mm3 are eligible if FIB-4 score \<3.5.
- History of biliary diversion
- Uncontrolled hypertension (either treated or untreated) defined as systolic blood pressure \>170 mmHg or a diastolic blood pressure \>100 mmHg at Screening
- Confirmed QTcF \>450 msec for males and \>470 msec for females at the Screening ECG assessment;
- Presence of sustained atrial fibrillation at time of Screening or history of paroxysmal atrial fibrillation episodes for the last 3 months prior to Screening
Where
- Peoria, Arizona
- Oxnard, California
- Fort Myers, Florida
- Riverview, Florida
- University Park, Florida
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Oct 16, 2026 · Source of record for eligibility and locations